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Originl Pper Med Princ Prct 2003;12:184 188 DOI: 10.1159/000070757 Received: Decemer 15, 2001 Revised: Decemer 21, 2002 A Study of Serologicl Mrkers of Heptitis B nd C Viruses in Istnul, Turkey S. Erden S. Büyüköztürk S. Çlngu G. Yilmz c S. Plnduz S. Bdur c Deprtments of Internl Medicine, Clinicl Infectious Diseses nd c Microiology, Fculty of Medicine, Istnul University, Istnul, Turkey Key Words Heptitis B surfce ntigen W Anti-HBs W Anti-heptitis C virus W Heptitis B mrker W Heptitis C mrker Astrct Ojective: This study ws undertken to investigte the prevlence of HBsAg, nti-hbs nd nti-hcv positivity in Istnul, Turkey. Sujects nd Methods: The frequencies of HBsAg, nti-hbs nd nti-hcv positivity were determined in 1,157 rndomly selected ptients ttending the outptient clinic of Istnul University Hospitl, Istnul, Turkey, during the yers 1998 nd 2001. All ptients underwent complete physicl nd vrious routine lortory exmintions. Results: Of the 1,157 ptients, the prevlence of HBsAg, nti-hbs nd nti-hcv ws 6.6, 28.1 nd 2.4%, respectively. It ppered tht hving dentl nd surgicl procedures formed the risk fctors for HBV infection. HBsAg positivity in the helth cre workers ws not different from tht of the other professions, ut nti-hbs ws significntly higher in this group. Conclusions: Our findings indicte tht HBV infection occurs more frequently thn HCV in Istnul, nd this poses n importnt helth prolem in the community. Copyright 2003 S. Krger AG, Bsel Introduction Virl heptitis which is widely seen ll over the world is one of the most importnt helth prolems in Turkey. Approximtely 200,000 people suffer cute virl heptitis in Turkey ech yer, nd out 4 million people re heptitis virus crriers [1]. A routine heptitis B vccintion progrm for neontes ws estlished in 1998. Its ppliction rte is pproximtely 81% for the whole country. Mny investigtions hve een done on the prevlence of heptitis B (HBV) nd heptitis C (HCV) infections in Turkey. Most of these studies were conducted on lood donors nd the results otined from different regions of Turkey showed some differences s for exmple, 10.8% heptitis B surfce ntigen (HBsAg) positivity reported in 1991 from Eskisehir nd 2.4% in 1994 from Izmir [1]. In this study, we imed to determine HBsAg, nti-hbs nd nti-hcv prevlence in popultion consisting of ptients who ttended the outptient clinic of the Deprtment of Internl Medicine, University Hospitl, Istnul, Turkey. ABC Fx + 41 61 306 12 34 E-Mil krger@krger.ch www.krger.com 2003 S. Krger AG, Bsel 1011 7571/03/0123 0184$19.50/0 Accessile online t: www.krger.com/mpp Dr. Sükrü Plnduz Istnul University, Istnul Medicl Fculty Deprtment of Internl Medicine, Division of Medicl Genetics Cp, Istnul 34093 (Turkey) Fx +90 212 4111393, E-Mil splnduz@istnul.edu.tr

Sujects nd Methods In the present study, 1,404 sujects were exmined over period of 3 yers, etween 1998 nd 2001, pproximtely 300 ptients per dy. The study group ws rndomly selected mong those ptients who cme to the outptient clinic for vrious resons, nd those who cme specificlly to e checked for heptitis. Ptients consent ws otined verlly. Two hundred nd forty-seven ptients with heptic disese nd HBV vccintion or who were close reltives of HBV crriers were initilly entered in the study, ut were susequently nlyzed seprtely. Of the remining 1,157 sujects, 371 were orn in Istnul nd 786 in other prts of the country; 836 were femle nd 321 mle. Age rnge of the ptients ws 15 85 yers, with n verge of 37.6 B 16.2. Averge ge of femles ws 38.5 B 15.8 yers, nd tht of mles ws 35.7 B 16.9 yers. All ptients hd undergone complete physicl exmintion nd routine lortory exmintions. A previously descried micro-elisa method ws used to nlyze for HBsAg, nti-hbs nd nti-hcv [2]. Whole lood smples were drwn nd clotted; the ser were seprted y centrifugtion nd stored t 2 8 C for up to 7 dys. Hepnostic HBsAg, Hepnostic Tle 1. The distriution of sujects ccording to gender Serologic mrker Mle (n = 321) Femle (n = 836) Totl (n = 1,157) HBsAg 39 (12.1%) d 38 (4.5%) 77 (6.6%) Anti-HBs 79 (24.6%) 247 (29.5%) 326 (28.1%) Anti-HCV c 12 (3.7%) 16 (1.9%) 28 (2.4%) Mle vs. femle HBsAg: p! 0.0001 (extremely significnt). Mle vs. femle nti-hbs: p = 0.093. c Mle vs. femle nti-hcv: p = 0.086. d The percentge in prentheses reltes to the totl numer of ptients in tht gender group. nti-hbs nd UBIHCV E1A 4.0 kits (Orgnon, Teknik) were used for testing the serologicl mrkers. The elements of qulity control progrm for ELISA were included with in-run nd etween-run control mesurements. The results otined were nlyzed with SPSS version 7.0 [3]. Descriptive nlysis ws used to find out the rtes of serologicl mrkers. Prevlence rtes of HBsAg positivity, nti-hbs nd nti-hcv were nlyzed ccording to ge, risk, professionl ckground nd geogrphicl region of irth. The risks used for clssifiction were undergoing dentl procedures, surgery, gynecologicl interventions, hving lood trnsfusion, working in the helth cre sector nd eing relted to crriers. The results of these sugroups were compred with Fisher s exct test. Results Among the totl ptient popultion of 1,404, group of 247, with history of heptitis or close reltionship with HBV crriers, hd HBsAg rte of 33.4% nd therefore were excluded from further sttisticl nlysis. Of the remining 1,157 ptients, HBsAg positivity ws found in 77 cses (6.6%), nti-hbs positivity in 326 persons (28.1%), nd nti-hcv positivity in 28 (2.4%). The rte of HBsAg in mles nd femles ws 12.1 nd 4.5%, respectively (p! 0.0001). The corresponding rte of nti- HBs in mles nd femles ws 24.6 nd 29.5% (p = 0.093) while the rte of nti-hcv in mles ws 3.7% nd in femles 1.9% (p = 0.086; tle 1). The prevlence of serologicl mrkers y ge is shown in tle 2. The highest HBsAg positivity rte (9.6%) ws in group II (21 40 yers). In contrst, nti-hbs nd nti- HCV rtes were highest in the ge-group III (41 60 yers). HBsAg prevlence in the ge-group of 21 40 yers ws significntly higher thn tht in the ge-group of 0 20 yers nd in those ged 61 nd over. Tle 2. The ge distriution of ptients Age-groups HBsAg Significnce n % (group vs. men HBsAg) Anti-HBs n % Significnce (group vs. men nti-hbs) Anti-HCV n % Significnce (group vs. men nti-hcv) Totl I (! 20 yers) 5 2.8 p = 0.061 32 18.2 p = 0.0075(s) 2 1.1 p = 0.414 175 II (21 40 yers) 43 9.6 p = 0.0562 121 27 p = 0.664 4 0.8 p = 0.070 447 III (41 60 yers) 25 5.8 p = 0.645 142 33 p = 0.039(s) 16 3.7 p = 0.166 425 IV (161 yers) 4 3.6 p = 0.230 31 28.1 p = 0.828 6 5.4 p = 0.117 110 Totl 77 6.6 326 28.1 28 2.4 1,157 Group I vs. group II HBsAg: p = 0.004 (very significnt). Group II vs. group III HBsAg: p = 0.044 (significnt). Group III vs. group IV HBsAg: p = 0.361 (NS). Gives the percentge of the totl in tht ge-group. Serologicl Mrkers of HBV nd HCV Infections Med Princ Prct 2003;12:184 188 185

Tle 3. The distriution of sujects ccording to risk groups Risk groups HBsAg Anti-HBs Anti-HCV Dentl procedures (n = 158) 18 (11.3%) 75 (47.4%) 7 (4.4%) Surgery (n = 89) 9 (10.1%) 23 (25.8%) 3 (3.3%) Gynecologicl interventions (n = 15) 1 (6.6%) 7 (46%) 0 Blood trnsfusion (n = 4) 1 0 1 Helth cre workers (n = 109) 6 (5.5%) 52 (47.6%) 1 (0.9%) Reltives of HBV crriers (n = 247) 82 (33.4%) 57 (23.2%) 12 (4.8%) Ptients with multiple risk fctors (n = 143) 22 (15.3%) 77 (58.3%) 12 (8.3%) Ptients with no known risk fctors (n = 639) 29 (4.5%) 47 (8.2%) 4 (0.69%) Excluded from the sttisticl nlysis. The percentge vlue refers to the numer of ptients in tht risk group. Tle 4. The distriution of sujects ccording to their professions Professions HBsAg Anti-HBs Anti-HCV Officils, employees (n = 230) 23 (10%) c 60 (26.1%) 12 (5.2%) Helth cre workers (n = 109) 7 (6.4%) 52 (47.7%) 1 (0.9%) Housewives (n = 526) 27 (5.1%) 157 (29.9%) 12 (2.3%) Techers (n = 75) 5 (6.6%) 21 (28%) 0 Students (n = 190) 7 (3.4%) 30 (17.6%) 2 (1.1%) Policemen (n = 27) 8 (29%) 6 (27.2%) 1 (3.7%) Totl (n = 1,157) 77 (6.6%) 326 (28.1%) 28 (2.4%) Helth cre workers nti-hbs vs. men nti-hbs: p! 0.0001. Students nti-hbs, vs. men nti-hbs: p = 0.0026. Other comprisons re not significnt. c The percentge vlue reltes to the totl numer of ptients in tht professionl group. Tle 5. The distriution of sujects ccording to the plces of irth Plce of irth HBsAg Anti-HBs Anti-HCV Mrmr region (n = 371) 17 (4.5%) 106 (28.5%) 7 (1.8%) Ege region (n = 49) 2 (4%) 12 (24.4%) 2 (4%) Mediterrnen region (n = 38) 2 (5.2%) 10 (26.3%) 2 (5.2%) Blck Se region (n = 274) 20 (7.3%) 66 (24%) 8 (2.9%) Middle Antoli (n = 139) 9 (6.4%) 38 (27.3%) 2 (1.4%) Estern Antoli (n = 153) 12 (7.8%) 44 (28.7%) 4 (2.6%) Southestern Antoli (n = 79) 10 (12.6%) 28 (35.4%) 1 (1.2%) Bulgri (n = 54) 5 (9.2%) 22 (40.7%) 2 (3.7%) Totl (n = 1,157) 77 (6.6%) 326 (28.1%) 28 (2.4%) Mrmr region vs. southestern Antoli HBsAg: p = 0.015. The percentge reltes to the totl numer of ptients orn in the corresponding re. 186 Med Princ Prct 2003;12:184 188 Erden/Büyüköztürk/Çlngu/Yilmz/ Plnduz/Bdur

The distriution of sujects ccording to risk groups is shown in tle 3. HBsAg positivities in ptients who hd surgicl opertion nd dentl intervention previously were higher thn the men HBsAg prevlence of the ptients with no risk (p = 0.03, p = 0.002). Anti-HBs positivity rtes in the ptients who hd dentl procedures, surgery, gynecologicl interventions, nd in helth cre workers were significntly higher thn the men nti-hbs rte for ll groups. Anti-HCV showed similr pttern s nti- HBs for ptients who hd dentl procedures nd surgicl opertions. The HBsAg prevlence in the ptients with multiple risk fctors ws significntly higher thn in those with no known risk (p! 0.0001). The distriution of sujects ccording to professions is shown in tle 4. For HBsAg, no significnt difference ws oserved etween the vrious professionl groups, except for the policemen who were mostly from southestern Antoli with high rte of HBV infection. Helth cre workers showed significntly higher nd students lower nti-hbs positivity rte thn the other professions. The distriution of sujects ccording to plces of irth is given in tle 5. The highest HBsAg positivity rtes (12.6 nd 9.2%) were found in those from southestern Antoli nd those who migrted from Bulgri nd the lowest rte (4%) in those who were orn in the Aegen region. The HBsAg rte in the people from southestern Antoli ws significntly higher thn tht in people from the Mrmr region (p = 0.015). Discussion The heptitis B infection is mong the importnt community helth prolems in Turkey [4]. Although n extensive vccintion progrm for neontes ws estlished in 1998, its enefits hve not een chieved yet. In our study, the rte of HBV crriers in popultion of 1,157 ws found to e 6.6%. This vlue is consistent with some previous findings reported in Turkey [1]. As our study popultion consisted of ptients living in Istnul most of whom cme from different prts of the country, our results re expected to show some differences from the men rtes oserved for different regions of the country. In the norml popultion, HBsAg positivity of 3.4 nd 14% ws reported from Izmir in 1995 nd from Gzintep in 1996, respectively [1]. A study of pregnnt women in 1995 reported the HBsAg prevlence to e 4.2% [5]. It is ccepted tht in Turkey, the rte of HBsAg positivity, sed on the use of the ELISA method, is etween 3.9 nd 12.5% [1]. On the sis of these rtes, Turkey is included in the medium endemicity region. Of the countries with which Turkey hs frontiers, Cyprus, Irq, nd the United Ar Emirtes hve intermedite endemicity, while Bhrin, Irn, Isrel nd Kuwit re res of low endemicity [6]. In this study, HBsAg positivity incresed with ge (tle 2); this finding is similr to the previous studies in Istnul where the heptitis A seroprevlence incresed with ge while heptitis B seroprevlence hd not chnged [7, 8]. These findings indicte the importnce of horizontl trnsmission of HBV [8]. It is known from previous studies tht eing the reltive of HBV crrier constitutes the highest risk fctor for HBV infection [9]. In our study, in 247 ptients who were close reltives of heptitis B crriers, the HBsAg positivity ws 33.4% consistent with the previous report [9]; pprently horizontl contmintion tkes the led in terms of HBV infection in Turkey s previously reported [6]. The risk of infection ws lso high within the fmilies who live together in crowded homes, prticulrly in those prts of the society with low socioeconomic levels (tle 4). The helth cre workers, who re considered to e mong the importnt risk groups in terms of HBV infection [10, 11], did not show sttisticlly significnt vrition from other groups in terms of HBsAg positivity (tle 3). Anti-HBs positivity (47.6%) ws significntly higher thn the men nti-hbs rte (28.1%, p! 0.0001). According to pulished study, the rtes of HBsAg positivity in the helth cre workers in Turkey vry etween 2.0 nd 14.3%, similr to our result of 5.5%, nd nti-hbs positivity rtes etween 11.4 nd 56%, lso consistent with our finding of 47.6% [1]. Despite numer of protective mesures tken ginst HBV nd HCV infections in hospitls nd other helth institutions, it is ovious tht sufficient level of protection hd not een chieved. For exmple, in this study, the rte of heptitis B vccintion mong helth cre workers ws 11% (12/109), nd in ll the sujects, it ws 4.5%. This is pprently unstisfctory. The HBsAg positivity (12.6%, tle 5) of this study in southestern Antoli is similr to tht reported previously (14.3%) [1] ut the nti-hbs (35.4%) is lower thn the 50% reported in Gzintep, ig city in southestern Antoli [1]. In these prts of the country, people tend to live together s crowded fmilies nd snitry fcilities re still fr from dequte, fctor tht mkes the contmintion esier. Of the three mrkers, nti-hbs ws highest in ll regions, indicting tht HBV infection occurs more frequently in these regions thn HCV. Serologicl Mrkers of HBV nd HCV Infections Med Princ Prct 2003;12:184 188 187

When our ptients were clssified ccording to the risk fctors, those with history of surgicl opertions (p! 0.0001), dentl interventions (p = 0.001) nd multiple risk fctors (p! 0.0001) showed significntly higher nti- HCV prevlence thn the ptients with no known risk. But like HBsAg, nti-hcv ws not high in helth cre workers. Conclusion The present findings showed tht HBV seroprevlence ws higher thn HCV seroprevlence in the popultion of Istnul included in this study, nd it tended to increse with ge. References 1 Bdur S: Virl Heptitis in Turkey; in Kilicturgy K (ed): Virl Heptitis. Istnul, Noel Tip Kitpevi, 2001, pp 15 22. 2 Crpenter AB: Enzyme linked immunossys; in Rose NR, Mcrio EC, Folds JD, Lne HC, Nkmur RM (eds): Mnul of Clinicl Lortory Immunology. Wshington, ASM Press, 1997, pp 20 29. 3 Nie NH, Hull CM, Jenkins JG, Steinrennr K, Bent DM: Sttisticl Pckge of the Socil Sciences, ed 2. New York, McGrw-Hill, 1975. 4 Uzunlimoglu O, Yurdydydin C, Cetinky H, Bozky H, Colkoglu S, Tnkurt E, Srioglu M, Ozenirler S, Akkiz H, Degertekin H, Okten A: Risk fctors for heptocellulr crcinom in Turkey. Dig Dis Sci 2001;46:1022 1028. 5 Kuru U, Turn O, Sglm Z, Ceyln Y, Nurluoglu M, Agcfidn A: Prevlence of heptitis virus infection in pregnnt women nd their fmilies. Eur J Microiol Infect Dis 1996;15: 248 251. 6 André F: Heptitis B epidemiology in Asi, the Middle Est nd Afric. Vccine 2000; 18(suppl 1):S20 S22. 7 Sidl M, Unuvr E, Oguz F, Cihn C, Onel D, Bdur S: Age-specific seroepidemiology of heptitis A, B, nd E infections mong children in Istnul, Turkey. Eur J Epidemiol 2001;17: 141 144. 8 Degertekin H, Tuzcu A, Ylcin K: Horizontl trnsmission of HBV infection mong students in Turkey. Pulic Helth 2000;114:411 412. 9 Dw MA, Sil IM, Wrflli MM, Mufth MI: Seroepidemiology of heptitis B virus mrkers mong hospitl helth cre workers: Anlysis of certin potentil risk fctors. Sudi Med J 2000;21:1157 1160. 10 Weiss Y, Rinovitch M, Chner Y, Noy D, Siegmn-Igr Y: Prevlence of heptitis B virus mrkers mong hospitl personnel in Isrel: Correltion with some risk fctors. J Hosp Infect 1994;26:211 218. 11 Al-Sohini MO, l-sheikh EH, l-blll SJ, Mirghni MA, Rmi S: Occuptionl risk of heptitis B nd C infections in medicl stff. J Hosp Infect 1995;31:143 147. 188 Med Princ Prct 2003;12:184 188 Erden/Büyüköztürk/Çlngu/Yilmz/ Plnduz/Bdur